Soltau Irina, Mudersbach Eileen, Geissen Markus, Schwedhelm Edzard, Winkler Martin S, Geffken Maria, Peine Sven, Schoen Gerhard, Debus E Sebastian, Larena-Avellaneda Axel, Daum Guenter
Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
PLoS One. 2016 Dec 14;11(12):e0168302. doi: 10.1371/journal.pone.0168302. eCollection 2016.
Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient's quality of life. Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD) and carotid stenosis (CS).
Serum was sampled from blood donors (controls, N = 174) and from atherosclerotic patients (N = 132) who presented to the hospital with either clinically relevant PAD (N = 102) or CS (N = 30). From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking) or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia). Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS) than high density lipoprotein-cholesterol (HDL-C). In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment.
Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C.
动脉粥样硬化改变是心血管疾病死亡的主要原因，严重损害患者生活质量。鞘氨醇-1-磷酸（S1P）是一种信号鞘脂，可调节潜在的促动脉粥样硬化和抗动脉粥样硬化过程。在此，我们研究血清S1P浓度是否与外周动脉疾病（PAD）和颈动脉狭窄（CS）相关。
从献血者（对照组，N = 174）和因临床相关PAD（N = 102）或CS（N = 30）到医院就诊的动脉粥样硬化患者（N = 132）中采集血清。对所有受试者，采用质谱法测定血清S1P，通过常规实验室检测确定血液参数。与对照组相比，在进行恢复血流的侵入性治疗前，动脉粥样硬化患者的血清S1P水平显著降低。这种差异无法用动脉粥样硬化的危险因素（老年、男性、高血压、高胆固醇血症、肥胖、糖尿病或吸烟）或合并症（慢性阻塞性肺疾病、肾功能不全或心律失常）来解释。受试者工作特征曲线表明，S1P比高密度脂蛋白胆固醇（HDL-C）更能提示动脉粥样硬化（PAD和CS）。在35例患者中，治疗后1至6个月再次测定血清S1P。在该组中，无论患者患有PAD还是CS，或接受开放手术还是血管内手术，治疗后血清S1P浓度均升高。治疗后S1P水平与治疗前测得的血小板数量高度相关。
我们的研究表明，人类PAD和CS与血清S1P浓度降低相关，且S1P在提示这些疾病方面可能比HDL-C具有更高的准确性。
